Great efforts have been devoted to the development of advanced systems and platforms to meet the growing demand of collecting, detecting, and processing biological samples from different sources, such as blood, biopsy samples, and tissue samples, etc. Among them, immunomagnetic systems (with magnetic nanoparticles and/or beads) and microfluidic chips (with special surface materials), to name a few, offer high sensitivity in collecting a biologic substance of interest (e.g., target proteins or cells of interest) from biological samples (such as tissues samples or blood samples drawn from a human subject, etc.).
Specificity of these systems and platforms normally lie in system design, which often takes advantage of binding affinity between targeted molecules of interests (such as targeted proteins present within a targeted cell or on the surface of a targeted cell) and specially-designed detection probes (e.g., antibodies, macromolecules, small molecules, nucleic acid and/or other materials). As an example, a microfluidic chip has been developed to detect circulating tumor cells (CTCs) in a human blood sample using anti-EpCAM antibody as a detection probe, which offers high specific binding affinity to epithelial cell adhesion molecules (EpCAM), as most circulating tumor cells are epithelial cells.
The shedding of cells, especially epithelial cells into blood circulation is an intrinsic property of a malignant tumor, and thus provides important information with regard to disease stage diagnosis, monitoring of treatment plans, and ultimate survival of cancer patients. For example, it was found that the number of some types of cells (e.g., circulating rare cells (CRCs), circulating tumor cells (CTCs), etc.) and other biological substance present in human blood samples are correlated with cancer metastasis (e.g., the aggressiveness of the tumor cells) as well as the efficacy of cancer therapy.
However, for most cancers, the corresponding circulating tumor cells (CTCs) shed in blood are very scarce, making it very difficult and technically challenging to detect, isolate, and collect these CTCs. Even for patients with late stage metastatic cancer, the number of CTCs present in blood may be as few as one CTC per 109 blood cells. An enrichment process is necessary. In addition, there is a need to remove nonspecific binding of blood cells and other substances to improve detection sensitivity and specificity.
Furthermore, major bottleneck of most systems for rare cell detection lies in imaging techniques after targeted biologics of interest (e.g., rare cells or CTCs) are collected. Most immunomagnetic systems and microfluidic platforms for collecting target proteins or cells require bulky and expensive equipment, such as automated staging microscopes, automated scanners (e.g., for scanning and autofocusing in microfluidic channels) and/or readers (e.g., for quantitating scanned images). Moreover, a minimum of several hours of labor-intensive manual inspection of collected biological samples and/or images by a trained specialist may still be required.
Therefore, there is a need for a simplified and less expensive system to collect and concentrate a biologic substance of interest for various applications, such as disease diagnosis, disease treatment monitoring, and drug screening.